A number of polymers undergo a phase separation in response to a change in environmental conditions, such as solution pH, ionic strength or temperature. For instance, some soluble polymers become insoluble when the solution temperature is changed only a few degrees. These polymers are said to possess a critical solution temperature (CST). A polymer possessing a lower critical solution temperature (LCST) becomes insoluble when the temperature of the solution is increased through a particular narrow temperature range. Conversely, a polymer possessing an upper critical solution temperature (UCST) becomes insoluble when the temperature of the solution is decreased through a particular narrow temperature range.
Polymers capable of phase changes in response to temperature changes have been described by Taylor in U.S. Pat. No. 3,421,892 for use in controlling a process relating to film developing. In Taylor, a layer of polymer changes permeability as a function of temperature. The polymers are layered between supporting color-sensitive silver halide layers and are selected and designed to control the diffusion rate of chemical dyes in order to improve color isolation and process speed. The polymer layers are substantially dye-permeable only in the hydrated state. This results in an overall film development process that is substantially independent of temperature. Suitable polymers for use within the layers are identified as polyvinyl amides and, most preferably, polyacrylamides, including a variety of N-substituent groups. The N-substituents are selected, balancing hydrophilic groups that cause swelling as a function of the solubility of that group in a given solvent with hydrophobic groups which modulate the swelling so that at some definite ratio of hydrophilic to hydrophobic groups, the resultant compound will have the desired temperature-inverting properties. The Taylor polymers are designed to avoid extreme inverse temperature characteristics, since the purpose of the barrier is to be functionally compatible with the temperature-permeation properties of the rest of the photosensitive unit. One disadvantage of the polymers disclosed by Taylor is that they are not in a cross-linked form, and therefore require a supporting structure. Thus, they cannot conveniently be used as a permeation barrier independent of a solid-phase support.
Lim, in U.S. Pat. No. 4,407,957, describes suspending cells in a polyalginate solution and adding the suspension dropwise into a solution containing calcium ions that gels the alginate and encapsulates the cells. A membrane is deposited through interaction of a polymer which has an opposite charge (positive charge) with the gel particle itself. This interaction results in a polyelectrolyte complex skinned membrane on the gel surface. The gel entrapping the cells may be redissolved by exchanging the calcium ions in the gel with a Na.sup.+ ion, thus promoting diffusion of metabolites through the ionically "cross-linked" membrane encapsulating the cells. Lim describes injecting such a gel material, including encapsulated insulin into a mammalian body, for example. The gel is said to release insulin into the body over time as it diffuses through the gel pores.
Cussler, in U.S. Pat. No. 4,555,344, describes using a cross-linked ionic polymer gel, such as partially hydrolyzed polyacrylamide or dextran, to selectively absorb a low molecular weight solvent and solute from a solution that includes higher molecular weight components in the solution. The gel is introduced into the solution in a shrunken state. A pH change or a change in composition of the solution is required to cause the gel to rapidly swell in volume, absorbing low-molecular weight solvent and solute.
Graham, in U.S. Pat. No. 4,584,188, describes gels comprising a polymerizable cyclic (thio) ether and a hydrophilic homo- or copolymer. A temperature change is required for expelling or releasing from the gel an active substance previously absorbed from a solution.
A limitation to date regarding the use of polymer gels that change phases in response to a change in environmental conditions has been that separations from or deliveries to solutions have been substantially nonspecific. Both the Cussler and the Graham inventions rely upon a temporary physical entrapment of the solution or solvent within the gel. That is, a CST gel, for example, in response to a change in temperature through the CST absorbs a liquid to which it has been exposed. The solution is absorbed by the gel nonspecifically, only excluding molecules too large for its pore structure.
Consequently, there exists a need in the art for an improved system for controlling biological or chemical reactions in selected environments by providing methods of separating certain desired substances from a solution, delivering certain selected substances to, or exposing certain selected substances to a desired environment, which methods are readly and efficiently controllable. The present invention fulfills this need and further provides other related advantages.